This proposal describes development of computational methods and software to study metalloprotein active sites, and applications to a number of specific proteins. The methods include correlated ab initio quantum chemistry with large basis sets, continuum solvation models based on a self-consistent reaction field formalism, and mixed quantum mechamcal/molecular techniques. New algorithmic approaches, with demonstrated improvements in computational efficiency and accuracy, are described in each of these areas. Applications include studies of electron transfer in the photosynthetic reaction center, catlyatic mechanisms of the enzymes methane monooxygenase and ribonucleotide reductase, and redox potentials of iron sulfur proteins.